Demyelination but no cognitive, motor or behavioral deficits after adenovirus-mediated gene transfer into the brain

Fathallah‐Shaykh, Hassan M.; Ai, Kafrouni; Zhao, Liang; Ja, Garcia; Wh, Frawley; Forman, James

doi:10.1038/sj.gt.3301346

Cited by 10 publications

(8 citation statements)

References 20 publications

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“…This approach alleviates problems associated with existing methods for inhibiting apoptosis, including limited delivery into the cell, repeated or chronic injection/infusion protocols, and lack of specificity to apoptotic pathways. Over the past two years, several studies reported the use of replication-deficient viral-mediated gene transfer to successfully overexpress a number of proteins in the CNS (Choi-Lundberg et al, 1997;Bemelmans et al, 1999;Franklin et al, 1999;Kitagawa et al, 1999;Bohn et al, 2000;Eberhardt et al, 2000;Fathallah-Shaykh et al, 2000;Huber et al, 2000;Kordower et al, 2000;Watabe et al, 2000;Yagi et al, 2000;Yukawa et al, 2000;Boer et al, 2001;Watabe et al, 2001). Recombinant adenovirus gene transfer has also been used to express functional proteins in the spinal cord (Smith et al, 1996;Smith et al, 1997;Romero and Smith, 1998;Smith and Romero, 1999;Romero et al, 2000).…”

Section: Therapeutic Interventions: Delivery Of Anti-apoptotic Genes mentioning

confidence: 99%

Apoptotic Cell Death Following Traumatic Injury to the Central Nervous System

Springer¹

2002

BMB Reports

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Apoptotic cell death is a fundamental and highly regulated biological process in which a cell is instructed to actively participate in its own demise. This process of cellular suicide is activated by developmental and environmental cues and normally plays an essential role in eliminating superfluous, damaged, and senescent cells of many tissue types. In recent years, a number of experimental studies have provided evidence of widespread neuronal and glial apoptosis following injury to the central nervous system (CNS). These studies indicate that injury-induced apoptosis can be detected from hours to days following injury and may contribute to neurological dysfunction. Given these findings, understanding the biochemical signaling events controlling apoptosis is a first step towards developing therapeutic agents that target this cell death process. This review will focus on molecular cell death pathways that are responsible for generating the apoptotic phenotype. It will also summarize what is currently known about the apoptotic signals that are activated in the injured CNS, and what potential strategies might be pursued to reduce this cell death process as a means to promote functional recovery.

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Section: Therapeutic Interventions: Delivery Of Anti-apoptotic Genes mentioning

confidence: 99%

Apoptotic Cell Death Following Traumatic Injury to the Central Nervous System

Springer¹

2002

BMB Reports

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“…In this study, we only examined the efficacy of adenoviral gene transfer during a 7-day interval because of the poor cell status from the seventh day post-infection onward. One possible explanation is the adenoviral vector itself, which is known to induce an immune response that prevents long-term expression of transgenes (Wood et al 1996;Barkats et al 1998;Thallah-Shaykh et al 2000). In spite of immunotoxicity and restricted efficacy in the usage of the adenoviral vector for gene transfer to the CNS, the adenovirus-based RNAi can improve gene-silencing efficiency by effectively transfecting neurocytes, relative to nucleofection with pSIREN-mdr1b1.…”

Section: Discussionmentioning

confidence: 97%

Reversal of Mdr1b-dependent Multidrug Resistance in a Rat Astrocyte Model by Adenoviral-delivered Short Hairpin RNA

et al. 2008

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Over-expression of P-glycoprotein (Pgp), a protein responsible for multidrug resistance (MDR), is responsible for general resistance to anti-epileptic drugs (AEDs). We explored the potential use of gene therapy with adenoviral-delivered RNA interference against mdr1b as a method to sensitize refractory epilepsy to AEDs. We constructed replication-deficient recombinant adenovirus Adeno-mdr1b1 carrying short hairpin RNA (shRNA) targeting against mdr1b, and successfully infected the established Sprague-Dawley rat astrocyte model of Coriaria Lactone-induced Pgp over-expression. The expression levels of mdr1b and Pgp and the Rhodamine123 efflux ratio in trial groups were significantly lower than that of blank control (P \ 0.05) during the first 7 days post-infection, with the most inhibition at 48 h. The results suggest that knockdown of MDR using adenovirus not only avoided the toxicity and low rate of plasmid nucleofection, but also overcame its poor efficiency of mdr1b silencing.More importantly, this study may pave the way for a promising approach to remedy refractory epilepsy.

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“…For example, treatment with NGF or glucocorticoid increased transcription of the TH gene. Hypoxia has been reported to prolong the stability of TH mRNA 45, 46 and GDNF has been shown to regulate expression of the TH gene by a variety of mechanisms 47–51. Given the growing literature on the many different ways TH is regulated, it may not be surprising that its expression is modulated by introducing a viral vector, resulting in the associated injury.…”

Section: Discussionmentioning

confidence: 99%